Currently, component transfusion in which only blood components required for a patient are transfused is more popular in the field of transfusion. In component transfusion, leukocytes must be removed from various blood products to a level low enough to prevent side effects that may occur after transfusion. As a method for removing leukocytes, a filter method is widely accepted due to advantages such as excellent leukocyte removal capability, simple operation, and low cost.
In this case, a method of removing leukocytes using a filter after separating blood into each of its components and adjusting various blood component products requires a leukocyte removal operation for each blood component product. On the other hand, a method of adjusting each blood component product after removing only leukocytes from whole blood is very useful from the viewpoint of operability and cost, since only one leukocyte removal operation is necessary.
However, since currently commercially available filters for whole blood products also remove platelets, a platelet product cannot be prepared from a whole blood product obtained by filtration using these filters. Therefore, a high performance filter that can allow platelets and erythrocytes to pass through and selectively remove leukocytes is demanded.
There are several reports on filters to remove leukocytes from blood that can allow platelets and erythrocytes to pass through. Japanese Patent Publication No. 6-51060 discloses a filter containing a nonionic hydrophilic group and a basic nitrogen-containing functional group on the surface that can be prepared by coating with a copolymer containing hydroxyethyl methacrylate (hereinafter abbreviated as HEMA) and dimethylaminoethyl methacrylate. According to research conducted by the inventors of the present invention, the filter was found to have a problem of easily allowing polymers to be eluted in spite of its capability of allowing platelets to pass through due to the high hydrophilicity of the polymer. The present inventors have found that if hydroxypropyl methacrylate, which is a little more hydrophobic than HEMA, is used instead of the HEMA, the effect of preventing elution can be achieved. However, the filter encountered a new problem of decreasing the platelet recovery rate if the filter has been sterilized with high pressure steam.
The applicants of the present invention have disclosed, in Japanese Patent Application Laid-open No. 5-194243, a leukocyte-removing filter containing an ethylene oxide chain with 2-15 ethylene oxide repetitions and a basic nitrogen-containing functional group, in which the hydrophilicity is increased and the platelet recovery rate is improved by introducing the ethylene oxide chain onto the filter surface. However, the present inventors have found that elution of a polymer into blood may be anticipated, if the ethylene oxide chain is long or the content of the ethylene oxide chain is increased.
The applicants of the present invention have further disclosed a leukocyte-removing filter containing an ethylene oxide chain with two ethylene oxide repetitions in Japanese Patent Application Laid-open No. 2000-245833. However, this filter is also thought to have a risk of elution of a polymer into the blood due to the large content of ethylene oxide chain (14-38 wt %) in the polymer used in the examples.
Moreover, the applicants of the present invention have disclosed, in Japanese Patent Application Laid-open No.7-25776, a filter for selectively removing leukocytes with a polymer having both a hydrophobic moiety and an ethylene oxide chain with 2-100 ethylene oxide repetitions coated on the surface. The filter can remove leukocytes efficiently with little platelet adhesion, while inhibiting elution of polymers. However, the filter used in the examples may also have a risk of eluting the polymer into the blood due to the large content of ethylene oxide chain (59-74 wt %) in the polymer, although the polymer has hydrophobic moieties. In view of the fact that a polymer containing an ethylene oxide chain tends to be eluted at a low temperature rather than at a high temperature, the present inventors have investigated elution of a polymer containing methyl methacrylate (30 mol %) and methoxynonaethylene glycol methacrylate (70 mol %) with 9 ethylene oxide repetitions at a normal blood processing temperature (room temperature) and have found that 20% of the polymer was eluted. In addition, although high hydrophilicity is effective for suppressing platelet adhesion, a decrease in leukocyte capturing capability is anticipated. This problem did not surface in the patent specification due to the use of a concentrated platelet solution with a low leukocyte concentration in the examples. The present inventors have found that sufficient leukocyte removal capability cannot be obtained if whole blood with an overwhelmingly high leukocyte concentration as compared with a concentrated platelet solution is used.
There have been no filters for selective removal of leukocytes having excellent sterilization resistance, high safety due to the least elution of polymers into the blood, and high blood processing performance.